Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000166919 | SCV000217738 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-28 | criteria provided, single submitter | clinical testing | The p.H96Y variant (also known as c.286C>T), located in coding exon 3 of the SDHAF2 gene, results from a C to T substitution at nucleotide position 286. The histidine at codon 96 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001248062 | SCV001421526 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 96 of the SDHAF2 protein (p.His96Tyr). This variant is present in population databases (rs755605816, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SDHAF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 187214). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Baylor Genetics | RCV004567320 | SCV005056610 | uncertain significance | Paragangliomas 2 | 2024-02-23 | criteria provided, single submitter | clinical testing |